过氧化物酶体增值物激活受体-γ2基因启动子区C-689T多态性与汉族人群冠心病的相关性

黎简平; 傅永平; 常文秀; 易昌容; 刘丽华; 邢海燕

doi:10.24920/J1001-9294.2017.042

Your Location：

Home >

Browse articles >

过氧化物酶体增值物激活受体-γ2基因启动子区C-689T多态性与汉族人群冠心病的相关性

中国医学科学杂志（英文版） 2017年32卷第3期页码：177-184

Orginal Article | Updated：2024-04-10

- 过氧化物酶体增值物激活受体-γ2基因启动子区C-689T多态性与汉族人群冠心病的相关性
- Affiliations：
  
  1. 1Department of Cardiovascular Internal Medicine, Affiliated Hospital of Shaoxing University, Xiaoxing, Zhejing 312000, China
  2. 2Laboratory of Molecular Biology, Medical College of Shaoxing University, Shaoxing, Zhejiang 312000, China
  3. 3Department of Statistics, Medical College of Shaoxing University, Shaoxing, Zhejiang 312000, China
- Author bio：
  
  *Corresponding author Tel: 86-15906856131, E-mail: lijianping123456@sina.com
- Funds：
- DOI：10.24920/J1001-9294.2017.042
  中图分类号：
- 收稿日期：2016-06-02，
  
  网络出版日期：2017-09-26，
  
  纸质出版日期：2017-09
- Accepted：
Scan QR Code
黎简平, 傅永平, 常文秀, 等. 过氧化物酶体增值物激活受体-γ2基因启动子区C-689T多态性与汉族人群冠心病的相关性[J]. 中国医学科学杂志（英文版）, 2017,32(3):177-184.

Li Jian-ping, Fu Yong-ping, Chang Wen-xiu, et al. Functional Variant of C-689T in the Peroxisome Proliferator-Activated Receptor-γ2 Promoter is Associated with Coronary Heart Disease in Chinese Nondiabetic Han People[J]. Chinese medical sciences journal, 2017, 32(3): 177-184.
黎简平, 傅永平, 常文秀, 等. 过氧化物酶体增值物激活受体-γ2基因启动子区C-689T多态性与汉族人群冠心病的相关性[J]. 中国医学科学杂志（英文版）, 2017,32(3):177-184. DOI： 10.24920/J1001-9294.2017.042.

Li Jian-ping, Fu Yong-ping, Chang Wen-xiu, et al. Functional Variant of C-689T in the Peroxisome Proliferator-Activated Receptor-γ2 Promoter is Associated with Coronary Heart Disease in Chinese Nondiabetic Han People[J]. Chinese medical sciences journal, 2017, 32(3): 177-184. DOI： 10.24920/J1001-9294.2017.042.

摘要

目的

研究过氧化物酶体增殖物激活受体-γ2（PPAR-γ2）基因启动子区C-689T多态性与冠心病的相关性。

方法

本病例对照研究在中国汉族非糖尿病人群中纳入455例冠心病患者作为病例组，693名健康体检者作为对照组。以问卷的形式采集受试者吸烟、饮酒、体育活动的情况；测量身高、体重、腰围及血压，计算体重指数（BMI）；测定空腹血糖、总胆固醇和甘油三酯水平。采用聚合酶链反应限制性片段长度多态性检测PPAR-γ2基因启动子区C-689→T突变。分析病例组和对照组间不同基因型的分布差异，并比较两组间的基因型、临床测量指标、实验室检查指标的差异，采用单因素和多因素回归分析基因型对冠心病风险的影响。

结果

病例组的C-689T多态性CC，CT和TT基因型频率分别为89.7%

9.9%和0.4%，对照组分别为 93.1%，6.6%和0.3%，两组的分布差异有显著性 (CC比CT+TT，γ

=6.243，P=0.041)。-689T等位基因携带者（n=95）的总胆固醇水平显著高于非携带者(n=1053，5.12±1.26比4.76±1.22 mmol/L，P=0.001)。男性-689T等位基因携带者(n=51)比男性非携带者(n=656)的腰围更大、体重更重、总胆固醇和甘油三酯水平更高(均P

0.05)。在肥胖者 (BMI≥25 kg/m2)中，-689T等位基因携带者(n=82)与非携带者(n=231)比较，腰围和BMI更大、收缩压和总胆固醇水平更高（P均

0.05）。在校正年龄、性别、腰围、体重、BMI、吸烟、身体活动、血压、空腹血糖、总胆固醇和甘油三酯后，-689T等位基因是冠心病的独立预测因子(OR=1.668，95%CI:1.031-2.705，P=0.037)。

结论

-689T等位基因可能与中国汉族人群冠心病高风险性相关。-689T等位基因与冠心病危险因素可能存在相关性。

Abstract

Objective

To investigate the association between the polymorphism of C-689T in the peroxisome proliferator-activated receptor-γ2 (PPARγ2) promoter and coronary heart disease (CHD).

Methods

This case-controlled study was conducted in nondiabetic Chinese Han people

which enrolled 455 patients with CHD (cases) and 693 subjects without CHD (controls). Data of clinical indexes were collected

including height

body weight

waist circumstance

systolic blood pressure (SBP)

diastolic blood pressure (DBP)

smoking

drinking

physical activity

as well as body mass index (BMI). Fasting blood glucose (FBG)

plasma total cholesterol (TC) and triglyceride (TG) levels were measured. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the PPARγ2 promoter C-689→T substitution. The genotype distribution of PPARγ2 promoter C-689T

allelic frequency

clinical indexes

and laboratorial measurements were compared between the two groups. The effect of genotype on the risk of CHD was assessed using univariate and multivariate regression model.

Results

The genotype frequencies of CC

CT and TT in PPARγ2 promoter C-689T were 89.7%

9.9% and 0.4% in the case group

and 93.1%

6.6% and 0.3% in the control group

respectively (CC

. CT+TT

= 6.243

=0.041). Carriers of -689T allele (

=95) had significantly higher TC level than non-carriers (

=1053) (5.12±1.26

vs.

4.76±1.22 mmol/L

=0.001). Male carriers of -689T allele (

=51) were significantly higher in waist circumference

body weight

TC and TG than male non-carriers (

=656) (all

0.05). In subjects whose BMI was over 25 kg/m

carriers of -689T allele (

=82) had significantly higher levels of waist circumference

BMI

SBP and TC than non-carriers (

=231) (all

0.05). The -689T allele was an independent risk factor for CHD (

=1.668

95%

: 1.031-2.705

=0.037) after adjusting for age

gender

waist circumference

body weight

BMI

smoking

physical activities

SBP

DBP

FBG

TC and TG level.

Conclusion

These data support the hypothesis that the -689T allele is associated with an increased risk of CHD

in Chinese Han people and correlates significantly with the profiles of CHD-related risk factors.

关键词

Keywords

references

Desvergne B , Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999 ; 20 ( 5 ): 649 - 88 . doi: 10.1210/edrv.20.5.0380 10.1210/edrv.20.5.0380 .

Fajas L , Auboeuf D , Raspé E , Schoonjans K , Lefebvre AM , Saladin R , et al. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem 1997 ; 272 ( 30 ): 18779 - 89 . doi: 10.1074/jbc.272.30.18779 10.1074/jbc.272.30.18779 .

Wayman NS , Hattori Y , McDonald MC, Mota-Filipe H, Cuzzocrea S, Pisano B, et al. Ligands of the peroxisome proliferator-activated receptors (PPAR-γ and PPAR-α) reduce myocardial infarct size. FASEB J 2002 ; 16 ( 9 ): 1027 - 40 . doi: 10.1096/fj.01-0793com 10.1096/fj.01-0793com .

Choi D , Kim SK , Choi SH , Ko YG , Ahn CW , Jang Y , et al. Preventative effects of Rosiglitazone on restenosis after coronary stent implantation in patients with type 2 diabetes. Diabetes Care 2004 ; 27 ( 11 ): 2654 - 60 . doi: 10.2337/ diacare.27.11.2654 10.2337/ diacare.27.11.2654 .

Sidhu JS , Cowan D , Tooze JA , Kaski JC. Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces circulating platelet activity in patients without diabetes mellitus who have coronary artery disease. Am Heart J 2004 ; 147 ( 6 ): e25 . doi: 10.1016/j.ahj.2003.12.035 10.1016/j.ahj.2003.12.035 .

Meirhaeghe A , Tanck MW , Fajas L , Janot C , Helbecque N , Cottel D , et al. Study of a new PPARγ2 promoter polymorphism and haplotype analysis in a French population. Mol Genet Metab 2005 ; 85 ( 2 ): 140 - 8 . doi: 10.1016/j.ymgme. 2005.02.004 10.1016/j.ymgme. 2005.02.004 .

Meirhaeghe A , Cottel D , Amouyel P , Dallongeville J. Association between peroxisome proliferator-activated receptor gamma haplotypes and the metabolic syndrome in French men and women. Diabetes 2005 ; 54 ( 10 ): 3043 - 8 . doi: 10.2337/diabetes.54.10.3043 10.2337/diabetes.54.10.3043 .

Dallongeville J , Iribarren C , Ferrières J , Lyon L , Evana A

Go AS , et al. Peroxisome proliferator-activated receptor gamma polymorphisms and coronary heart disease. PPAR Res 2009 ; 2009 : 543746 . doi: 10.1155/2009/543746 10.1155/2009/543746 .

Shmueli E , Alberti KG , Record CO. Diacylglycerol/protein kinase C signaling: a mechanism for insulin resistance? J Intern Med 1993 ; 234 ( 4 ): 397 - 400 . doi: 10.1111/j.1365-2796.1993.tb00761.x 10.1111/j.1365-2796.1993.tb00761.x .

Kim HI , Kim JW , Kim SH , Cha JY , Kim KS , Ahn YH , et al. Identification and functional characterization of the peroxisomal proliferator response element in rat GLUT2 promoter. Diabetes 2000 ; 49 ( 9 ): 1517 - 24 . doi: 10.2337/dia betes.49.9.1517 10.2337/dia betes.49.9.1517 .

Jackson SM , Parhami F , Xi XP , Berliner JA , Hsueh WA , Law RE , et al. Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol 1999 ; 19 ( 9 ): 2094 - 104 . doi: 10.1161/01.ATV.19.9.2094 10.1161/01.ATV.19.9.2094 .

Straus DS , Pascual G , Li M , Welch JS , Ricote M , Hsiang CH , et al. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc Natl Acad Sci USA 2000 ; 97 ( 9 ): 4844 - 9 . doi: 10.1073/ pnas.97.9.4844 10.1073/ pnas.97.9.4844 .

Akiyama TE , Sakai S , Lambert G , Nicol CJ , Matsusue K , Pimprale S , et al. Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux. Mol Cell Biol 2002 ; 22 ( 8 ): 2607 - 19 . doi: 10.1128/MCB.22.8.2607-2619.2002 10.1128/MCB.22.8.2607-2619.2002 .

Marx N , Schonbeck U , Lazar M , Libby P , Plutzky J. Peroxisome proliferator-activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 1998 ; 83 ( 11 ): 1097 - 103 . doi: 10.1161/01.RES.83.11.1097 10.1161/01.RES.83.11.1097 .

Khodaeian M , Enayati S , Tabatabaei-Malazy O , Amoli MM. Association between genetic variants and diabetes mellitus in Iranian populations: a systematic review of observational studies. J Diabetes Res 2015 ; 2015 : 1 - 21 . doi: 10.1155/2015/585917 10.1155/2015/585917 .

Lavrenko AV , Shlykova OA , Kutsenko LA , Mamontova T , Kaidashev IP. Pharmacogenetic features of the effect of metformin in patients with coronary heart disease in the presence of metabolic syndrome and type 2 diabetes mellitus in terms of PPAR-gamma2 gene polymorphism. Ter Arkh 2012 ; 84 ( 9 ): 35 - 40 . doi: 10.17116/terarkh201284935-40 10.17116/terarkh201284935-40 .

浏览量

733

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

关联资源

暂无数据